Insecticidal bis-halophenyl di-fluoroaliphatic compounds



United States Patent Ofiice 3,021,358 Patented Feb. 13, 1962 3,021,358 INSECTICIDAL BIS-HALOPHENYL DI-FLUORO- ALIPHATIC COMPOUNDS Joseph Bornstein, Brighton, Mass., Murray S. Blum, Baton Rouge, La., and John J. Pratt, Jr., Wayland, Mass., assignors to the United States of America as represented by the Secretary of the Army No Drawing. Original application July 28, 1958, Ser. No. 751,579, now Patent No. 2,990,321, dated June 27, 1961. Divided and th'm application Jan. 29, 1960, Ser. No. 9,154

6 Claims. (Cl. 260-488) (Granted under Title 35, US. Code (1952), sec. 266) H FCF wherein Hal and Hal are halogen atoms of an atomic weight not above 80 -(i.e., fluorine, chlorine and bromine), and wherein Y is hydrogen, hydroxyl or acetoxyl. Compounds falling under this general formula are 2,2-difluoro-1,1-bis-(p-halophenyl) ethanes, 2,2-difiuoro-1,1-bis- (p-halophenyl)-ethanols, and 2,2-difluoro-l,l-bis-(p-halophenyD-ethyl acetates. Also within the purview of our invention are dehydrofluoro ethene analogs of 2,2-difiuoro-1,1-bis-(p-halophenyl)-ethanes, which analogs havethe general formula:

' HG F The foregoing compounds may be prepared by a Grignard type reaction, as will be more fully explained hereafter.

Tests have shown that among the foregoing compounds the 2,2-difluoro-1,l-bis-(p-halophenyl)-ethanols are highly potent insecticides, and are surprisingly and strikingly effective as synergists for DDT; these effects are particularly striking when the halogen atoms on the respective phenyl groups are either chlorine or bromine. However, the other compounds herein disclosed are likewise valuable weapons in the arsenal of economic entomology, in-

asmuch as experience has shown that succeeding generations of insects quickly acquire immunity to a given type of insecticide through the breeding of resistant strains. It is therefore important to have alternate insecticides and insecticidal. synergists on hand to combat insects which have thus acquired immunity against a previously very effective insecticide.

We are now aware (though this was not known to us at the outset of our research) that 2,2,2-trifluoro-l,1-bis- (p-halophenyl)-ethanes, ethanols and ethyl acetates have been disclosed as synergists for DDT (see Tahori in Journal of Economic Entomology, 1955, vol. 48, pp. 63 8-642, and Kaluszyner et al. in American Chemical Society Journal, 1955, vol. 77, pp..4164-4168); however, we have found surprisingly that our 2,2-difiuoro compounds have unexpectedly more powerful synergistic insecticidal action in combination with DDT than the results obtained by the foregoing workers with 2,2,2-trifluoro compounds would have permitted to expect.

We will now proceed to illustrate the practice of our inventionby means of several examples, but wish to have it understood that we do not intend to limit the practice of our invention to the particular methods therein set forth, inasmuch as our novel compounds can be made by other syntheses and may be combined with DDT in any desired proportion, as may be most effective under the circumstances of a particular application.

EXAMPLE 1 2,2-difluoro-1,I-bis-(p-chlorophenyl) -ethanol Freshly purified ethyl difluoroacetate (20.0 g., 0.16 mole), diluted with an equal volume of ether, was added with stirring in the course of 1 hr. to the ice-cold Grignard reagent prepared from 10.7 g. (0.44 g.-atom) of magnesium turnings and 81 g. (0.44 mole) of l-bromo- 4-chlorobenzene in ml. of ether. Stirring and cooling in the ice-bath were maintainedfor 2 hours after completion of the addition of the ester. The reaction mixture, after standing at room temperature overnight, was treated, while stirring and cooling, with saturated ammonium chloride, prepared by shaking 40 g. of the salt with 100 ml. of water. The yellow suspension was filtered with suction through a sintered-glass funnel, the filter cake was washed with ether, and the combined ethereal extract washed twice with water before being dried over sodium sulfate. Evaporation of the ether yielded a dark orange oil which was diluted-with an equal volume of methanol and refrigerated at 35 for 2 days in order to allow the traces of biphenyl to crystallize. Filtration of the mixture followed by steam distillation of the filtrate (2 l. of distillate was collected and discarded) gave a product which was essentially free of starting material and derived products. The oily residue was dissolved inether and dried over sodium sulfate. Removal of the solvent and distillation of the residue afforded a 53% yield of 2,2-difiuoro-1,1-bis-(p-chlorophenyl)-ethanol, a liquid having a RP. of 136 C. at 0.20 mm.; index of refraction n 1.5780. With concentration H 80 it gave a cherry-red color. Analysis c,,H,,c1,F,0

Upon prolonged standing, t-hick prisms formed, having a MP. of 54.5-56.0 C. 1

The m-chlorophenyl and o-chlorophenyl analogs are produced by substituting the same amounts of l-bromo- 3 4 3-chlorobenzene or l-bromo-Z-chlorobenzene in lieu of ethyl acetate was obtained in liquid form from the 2,2-dithe l-bromo-4-chlor0benzene of the above example. fluoro-1,l-bis-(p-fluorophenyl)-ethanol of Example 3; it EXAMPLE 2 resisted attempts to induce crystallization and isolated as a very viscous oil at 80 C. and 0.1 mm. pressure; index .2- fluo -L -(pp ybs of refraction u 1.5158. Analysis (c H Fpg: Example 1 was repeated, but a stoichiometrically equivalent amount 104 grams; 0.44 mole) of 1,4-dibromo- Calculated Found benzene was used in lieu of l-bromo-4-chlorobenzene. A 40% yield of 2,2-difluoro-l,1-bis-(p-bromophenyl)- 01.53 61.8 ethanol was obtained as a liquid which had a boiling point H of 153-164 C. at 0.17 mm.; index of refraction n 1.6039. With concentrated H 80 it gave a red color. EXAMPLE 5 Analys (CIIHMBHF'O): 2,2-difluor0-1,I-bis-(p-halophenyl)ethane 8.0-10.0 grams of 2,2 difluoro 1,1 bis (p chlorophenyD-ethanol (Ex. 1) were heated under reflux for ten days with a mixture of 33 g. of red phosphorus, 1.27 g. 3;; of iodine, so ml. of glacial acetic acid, and 1.0 ml. of 40.6 water. The cooled reaction mixture was filtered with suction directly into a separator ;l1 funnel containing 300 ml. of 2.5% sodium bisulfite. e only suspension was Upon prolonged g thick formed hams neutralized by adding portions of solid sodium bicarbona 545-56. ate with intermittent shaking and was then extracted with Calculated EXAMPLE 3 ether. The ether extract was dried over sodium sulfate after being washed with water. Removal of the ether 2.2- rfl r -1.I- ir-(p-fl p mI)- and distillation of the residue in vacuo yielded an oil Example 1 was repeated, but a stoichiomdficany equiw which spontaneously crystallized. The crude crystals alem amount (0 44 mole) of Lb I n I one were recrystallized by means of a methanol-water solvent,

I H u Q a aP and a 90% yield of 2,2-difluom-1,l-bis-(p-chlorophenyl)- ethane crystals having a M.P. of 37.5-38.5 C. and a yield of 2,2-d1fiuoro-l,l-bis-(p-fluorophenyl)-ethanol was a obtained in liquid form having a 13.1. of 99-100 0. at 25 9 9' mm was waned 0.05 mm.; index of refraction 1.5276. with con- 1 centrated H,S0 it gave a red orange color. Analysis 14 1o 4 was used in lieu of 1-bromo-4-chlorobenzene. A 43% Calculated Folmd 2,2-difluoro-l,l-bis-(pbromophenyl) ethane crystals were obtained in a 89% yield from the 2,2-difluoro-1,l-

EXAMPLE 4 bis-(p-bromophenyD-ethanol of Example 2 in the same way as the chloro analog; methanol was used as the sol- 2,2-difluoro-1,1-bis-(p-halophenyl)-ethyl acetate vent for recrystallization. M.P. 42.0-42.8 C. Analysis in. 2,2-difluoro-1,l-bis-(p-chl0rophenyl)-eth 1 of n m s m Ple 1 was permitted to stand at room temperature for several hours with a mixture of acetic acid and tri- Fmmd fluoro acetic anhydride, in accordance with the procedures generally set forth by Tedder in Chem. Revs. 55, 787 gg-g :2 (1955). The resulting product was extracted with petro- Br 4214s 4215 leum ether solvent and recrystallized. A 82% yield of 2,2-difluoro-l,1-bis-(p-chlorophenyl)-ethyl acetate crystained in the form of a viscous oil from the 2,2-difluoro- 1,1-bis-(p-fluorophenyD-ethanol of Example 3 in a 90% yield. It resisted attempts to crystallize; its B.P. is 79- 80' C. at 1.5 mm. pressure; index of refraction u 1.5179. Analysis (C H Fflr Calculated Found 55.01 3.60 as so Calculated Found 2,2-difluoro-1,1 bis (p bromophenyl) ethyl acetate crystals having a M.P. of 80-805 C. were obtained in the same manner in an 86% yield from the 2,2-difluoro- 1,1-bis-(p-hmmophenyD-ethanol of Example 2. Analysis EXAMPLE 6 Dehydrofluoridatian products-(CflflalhQCHF Z-fluoro-I ,1 -bis-(p-halophenyl) when:

3.8 grams of 2,2-difluoro-l,l-bis-(p-bromophenyl)-ethane (Ex. 5) were dehydrofluorinated (removal of 1 mole of hydrogen fluoride) by heating under reflux for 2.5 hours with 60 ml. of 2% ethanolic potassium hydroxide.

' The solvent was removed under reduced pressure and the An 89% yield of 2,2-difluoro-l,l-bis-(p-fluorophenyl)- residue extracted with several portions of ether. The

Calculated Found Calculated Fotmd C 47. 20 47. H 2. 55 2. 4 Br 44. 86 44. 7

Crystals of Z-fluoro-1,1-bis-(chlorophenyl)-ethene were obtained in the same manner from 2,2-difluoro-1,1-bis- (p-chlorophenyl)-ethane of Example 5, in an 85% yield; M.P. 78.0-79.5 C. Analysis (C l-1.01m):

Calculated llound Liquid Z-fluoro-1,1-bis-(p-fluorophenyl)ethene was obtained from 2,2-difluoro-L1-bis-(p-fluorophenyD-ethane in a 93% yield; B.P. 8182 C. at 1 mm. pressure, in-

den of refraction u 1.5481. Analysis (C I-1 B):

Calculated Folmd The following table (Table I) shows the biological results obtained by testing the foregoing compounds on houseflies.

The first column of test results indicates the lethal effect of our compounds, applied alone to ordinary DDT susceptible adult female houseflies which were 'eated topically by applying acetone solutions of the compounds to the thorax (1 microliter of the solutions were applied in each instance).

Mortality data were taken 24 hours after treatment of the flies. One hundred and sixty flies were used in each test-4 replicates of 20 flies each duplicated from 2 difierent fly populations. The quantity of test compound required to kill 50% of the test flies (LD-SO) was determined by plotting on a logarithmic scale percent mortality versus dose of test compound.

The second column of test results shows the synergistic 6 action of our compounds in combination with DDT, when applied to a DDT-resistant strain of adult female houseflies in the same manner. The ratio of fluoro compounds to DDT was one part of fluoro compound to 5 parts of DDT.

TABLE I DDT-Re- DDT-Sussistant oentible Flies, Flies, 1 Part Fluoro Fluoro Com- Compound pound, Alone 5 Parts DDT 2,2-Difluoro-1,l-bis-(n-chlorophenyD-ethane 2. 2 0.96 2,2 Drtluoro-1,1-bis-(p-chlorophenyl)-ethanol.. 3. 8 0. 62 .2,2-D1fluoro-1,l-bis-(p-chlorophenyl)ethyl acetate 9. 4 1. 6 2-Fluoro-1,1-bls-(n-chlorophen l)-ethene 22 11.5 2,2-Ditluoro-l,1-bis-(p-bromop enyl)-ethane 2. 1 0.96 2,2-Difluoro-1,1-bis-(p-bromphenyD-ethanol 4. 9 0. 56 2,2Dlfluoro-1,1-bis-(p-bromophenyD-ethyl acefate 9. 7 1. 7 2-Fluoro-1,l-bis-(p-bromopheuyl)-ethene 21) 7. 1 2,2-Dlfluor0-1,1-b1s-(p-fluorophenyD-ethane 5. 1 2,2-Difluoro-l,l-bis-(p-fluorophenyD-ethanoL. 7. 2 2. 8 2,2-Difluoro-1,1-bis-(p-fluorophenyD-ethyl acetate. 35 8. 5 2-Fluoro-1,1-bis-(n-fluorophenyD-ethene 18 28 Control: DDT alone 0.35 1 150 1 (No fluoro compound, 6 parts DDT.)

In a further control experiment with the DDT-resistant strain of flies, a mixture of 1 part of 1,1-bis- (p-chlorophenyl)-ethanol (DMC, a known DDT synergist) and 5 parts of DDT was found to have an LD5 of 3.9, which is less potent thanmost of our new compounds.

It appears from the foregoing test results that the compounds of the present invention are efiective as insecticides, even when applied alone to insects which have not 4 yet bred immunity to DDT, even though the quantity of in the foregoing table, a most surprising reduction of quantity of synergistic mixture (as compared with the quantity of DDT alone) results in efiective kills of DDT- resistant insect strains; (the effectiveness of the compositions being in inverseratio to their numerical LD5 ratings.) This is borne out by a control computation.

on the synergistic effect on a number of the above 2,2- difiuoro compounds, as compared with the synergistic effect with DDT of the corresponding 2,2,2-trifluoro compounds reported by Tahori, supra.

TABLE II 1 Part 1 Part 1 Part 2,2-Di 2,2,2-tri- 2.2.2411- Fluoro Fluoro Fluoro Compound Com pound Compound to 5 Parts to 1 Part to 10 Parts DDT DDT DDT- 2,2 Difluoro 1,1 bis (p-chloro- 171 2,2,2-Trifluoro 1,1 -bis (p-ehloro- 14 0 phenyD-ethane. phenyD-ethane. 2,2 Difluoro 1.1 bis -(p-chloro- 194 2,2,2 Trifluoro -1,1-'bis -(p-chloro- 25 15 phenyD-ethanol. phenyll-ethanol. 2,2 Difluoro -1,1 bis -(p-chloro- 71 2,2,2-Trifluoro 1J-bis-(p-chloro- 15 11 phenyll-ethyl acetate. phenyll-ethyl acetate. 2,2 Difluoro -l,1 bis (p-bromo- 2,2,2 trifiuoro -1,1 bis -(p-bromo- 10 0 phenyD-ethane. phenyD-ethane. 2,2 Difluoro 1,1 bis- (p-bromo- 2,2.2- Trifluoro 1,1 -bis-(p-bromo- 16 12 phenvD-ethanol. 169 phenyD-ethanol. 2,2 Difluoro -1,1 bis (p-bromo- 71 2,2,2- Trifiuoro -1,1 -bis- (p-bromo- 14 1O phenyll-ethyl acetate. phenyD-ethyl acetate. 2,2 Difluoro -1,1 bis -(p-fiuoro- 42 2,2,2-Trifluoro -1.1-bls -(p-fluoro- 10 10 phenyD-ethanol. phenyD-ethanol.

In the foregoing table, Tahoris definition of synergistic activity was used in lieu of an LD rating, namely the factor by which it is possible to reduce the amount of DDT and still obtain the same mortaility; for exampie, with 2,2,2- trifluoro-Ll-bise(p-chlorophenyl)-ethanol (bis-(p-chlorophenyl)-trifluoromethyl-carbinol) could be reduced 15 times (1:15). Thus a high numerical rating in Table 11 indicates a high degree of synergism. It

should be noted in this connection that the tests reported by Tahori, supra, were conducted on a DDT-resistant strain of Palestinian houseflies (T strain) which appear, by reason of Tahoris comparison of that strain with at Berkeley strain, to have less immunity to DDT than the DDT-resistant houseflies on which our tests were conducted.

For economic reasons it is advisable to apply our new insecticides, when used as the sole active ingredient or in synergistic combination with DDT, by the use of a proper solid or liquid diluent, e.g., of the type customarily used with DDT, such as carbon black, talc, pyrophyllite, hydrocarbon solvent, alcohol, or aqueous emulsion.

The term DDT, as used in the specification and claims, denotes dichlorodiphenyltrichloroethane (pure or technical grade).

It will thus be seen that we have provided a series of new insecticidal compounds which are particularly efiective as DDT synergists; they may be arranged as to the degree of synergistic efficiency in the following general order:

2,2-difluoro-l,l-bis- (p-halophenyD-ethanols 2,2-difluoro-l,1-bis- (p-halophenyD-ethanes 2,2-difluoro-l,l-bis-(p-halophenyl)-ethyl acetates 2-tluoro-l,1-bis (p-halophenyl) -ethenes Bromine and chlorine are generally superior to fluorine as synergistically eficient substituents in the phenyl groups of the abovenamed compounds; while the para position is generally preferred, the meta and ortho positions are not excluded from the purview of our invention.

Having thus described our invention and several modes by which the same may be carried into practice, it will 8 be clear that several modifications and changes thereof may be made without departing from the spirit of our invention or from the scope of the subjoined claims. We thus desire to claim our invention as broadly as the prior art and the essential features of our invention will permit, and to this end have appended the following claims.

We claim:

1. An insecticidal compound having the formula:

H FCF wherein Hal and Hal are halogen atoms having an atomic weight not above and wherein Y is a member of the group consisting of hydrogen, hydroxyl and acetoxyl.

2. The insecticidal compound 2,2-difluoro-l,l-bis-(pchlorophenyl)-ethane.

3. The insecticidal compound 2,2-difluoro-l,l-bis-(pchlorophenyl)-ethanol.

4. The insecticidal compound 2,2-difluoro-1,1-bis-(pchlorophenyD-ethyl acetate.

5. The insecticidal compound 2,2-difluoro-1,1-bis-(pbromophenyD-ethanol.

6. An insecticidal compound being a member of the group consisting of 2,2-difluoro-1,l-bis-(p-chlorophenyl)- ethane, 2,2-difluoro-l,l-bis-(p-chlorophenyl)-ethanol, 2, Z -difluoro-1,1-bis-(p-bromophenyl)-ethane, 2,2-difluorol,l-bis-(p-bromophenyl)-ethanol, 2,2-difluoro-1,1-bis-(pfluorophenyl)-ethane, and 2,2-difluoro-1,l-bis-(p-fluorophenyD-ethanql.

References Cited in the file of this patent UNITED STATES PATENTS 2,729,681 Wilson et al. Ian. 3, 1956 2,776,988 Craig et a1. Jan. 8, 1957 OTHER REFERENCES Nature, vol. 176, Aug. 6, 1955, p. 266 and 267. 

1. AN INSECTICIDAL COMPOUND H AVING THE FORMULA: 